Maxillofacial Plastic and Reconstructive Surgery

Korean Association of Maxillofacial Plastic and Reconstructive Surgeons (대한악안면성형재건외과학회)
권호 표지

Anti-tumor Effects of Vascular Endothelial Growth Factor Receptor-3 Inhibitor on Oral Cancer Cells

구강암 세포에서 혈관내피성장인자 수용체-3 억제제의 항종양 효과

  • Kim, Chan-Woo (Department of Oral and Maxillofacial Surgery, Gangneung-Wonju National University College of Dentistry) ;
  • Kim, Seong-Gon (Department of Oral and Maxillofacial Surgery, Gangneung-Wonju National University College of Dentistry) ;
  • Park, Young-Wook (Department of Oral and Maxillofacial Surgery, Gangneung-Wonju National University College of Dentistry)
  • 김찬우 (강릉원주대학교 치과대학 구강악안면외과학교실) ;
  • 김성곤 (강릉원주대학교 치과대학 구강악안면외과학교실) ;
  • 박영욱 (강릉원주대학교 치과대학 구강악안면외과학교실)
  • Received : 2012.07.11
  • Accepted : 2012.07.13
  • Published : 2012.07.31
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis and lymphangiogenesis including induction of endothelial cell proliferation, migration and capillary tube formation. E7080 (S1164, Selleck chemical, Houston, TX, USA) is a muti-targeted kinase inhibitor, which targets VEGF receptor-2, 3 (VEGFR-2, 3) and inhibits survival and proliferation of tumor cell. The purpose of this study was to determine the anti-tumor effect of E7080 on oral squamous cell carcinoma. Methods: An oral squamous cell carcinoma cell line, SCC-9 was used in this study. E7080 was applied to SCC-9 cells by 3 different concentrations (1, 5, 10 ${\mu}g/mL$). Control means no application of E7080. The cellular growth was evaluated by real-time cell electronic sensing and MTT assay. The signal transduction was evaluated by Western blotting. Results: In experimental group, SCC-9 cell proliferation was decreased and the VEGFR-3 downstream pathways were inhibited compared with control. Furthermore, increasing the concentration of E7080, the ability of E7080 to disturbance of SCC-9 cell proliferation was increased. Conclusion: Proliferation of SCC-9 cells was inhibited by E7080, which was through by inhibition of VEGFR-3 downstream pathway. In vivo study with E7080 will be required to provide therapeutic benefits in oral squamous cell carcinoma.

Keywords

References

  1. Glen H, Mason S, Patel H, Macleod K, Brunton VG. E7080, a multi-targeted tyrosine kinase inhibitor suppresses tumor cell migration and invasion. BMC Cancer 2011;11:309. https://doi.org/10.1186/1471-2407-11-309
  2. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249-57. https://doi.org/10.1038/35025220
  3. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86:353-64. https://doi.org/10.1016/S0092-8674(00)80108-7
  4. Kyzas PA, Stefanou D, Batistatou A, Agnantis NJ. Prognostic significance of VEGF immunohistochemical expression and tumor angiogenesis in head and neck squamous cell carcinoma. J Cancer Res Clin Oncol 2005;131:624-30. https://doi.org/10.1007/s00432-005-0003-6
  5. Kerbel RS. Tumor angiogenesis: past, present and the near future. Carcinogenesis 2000;21:505-15. https://doi.org/10.1093/carcin/21.3.505
  6. Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 2002;20:4368-80. https://doi.org/10.1200/JCO.2002.10.088
  7. Moser C, Lang SA, Stoeltzing O. The direct effects of anti- vascular endothelial growth factor therapy on tumor cells. Clin Colorectal Cancer 2007;6:564-71. https://doi.org/10.3816/CCC.2007.n.023
  8. Jakeman LB, Armanini M, Phillips HS, Ferrara N. Developmental expression of binding sites and messenger ribonucleic acid for vascular endothelial growth factor suggests a role for this protein in vasculogenesis and angiogenesis. Endocrinology 1993;133:848-59. https://doi.org/10.1210/en.133.2.848
  9. Shweiki D, Itin A, Neufeld G, Gitay-Goren H, Keshet E. Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J Clin Invest 1993;91: 2235-43. https://doi.org/10.1172/JCI116450
  10. Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995;146:1029-39.
  11. Masood R, Cai J, Zheng T, Smith DL, Hinton DR, Gill PS. Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF receptor-positive human tumors. Blood 2001;98:1904-13. https://doi.org/10.1182/blood.V98.6.1904
  12. Xia G, Kumar SR, Hawes D, et al. Expression and significance of vascular endothelial growth factor receptor 2 in bladder cancer. J Urol 2006;175:1245-52. https://doi.org/10.1016/S0022-5347(05)00736-6
  13. Su JL, Yen CJ, Chen PS, et al. The role of the VEGF-C /VEGFR-3 axis in cancer progression. Br J Cancer 2007;96:541-5. https://doi.org/10.1038/sj.bjc.6603487
  14. Park YW, Kwon KJ, Lee JW. Immunohistochemical study on expression of lymphangiogenic factors in oral cancer. J Korean Assoc Maxillofac Plast Reconstr Surg 2010;32:1-8.
  15. Karkkainen MJ, Mäkinen T, Alitalo K. Lymphatic endothelium: a new frontier of metastasis research. Nat Cell Biol 2002;4:E2-5. https://doi.org/10.1038/ncb0102-e2
  16. Matsui J, Yamamoto Y, Funahashi Y, et al. E7080, a novel inhibitor that targets multiple kinases, has potent antitumor activities against stem cell factor producing human small cell lung cancer H146, based on angiogenesis inhibition. Int J Cancer 2008;122:664-71. https://doi.org/10.1002/ijc.23131
  17. Ikuta K, Yano S, Trung VT, et al. E7080, a multi-tyrosine kinase inhibitor, suppresses the progression of malignant pleural mesothelioma with different proangiogenic cytokine production profiles. Clin Cancer Res 2009;15:7229-37. https://doi.org/10.1158/1078-0432.CCR-09-1980
  18. Matsui J, Funahashi Y, Uenaka T, Watanabe T, Tsuruoka A, Asada M. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin Cancer Res 2008;14:5459-65. https://doi.org/10.1158/1078-0432.CCR-07-5270
  19. Ogino H, Hanibuchi M, Kakiuchi S, et al. E7080 suppresses hematogenous multiple organ metastases of lung cancer cells with nonmutated epidermal growth factor receptor. Mol Cancer Ther 2011;10:1218-28. https://doi.org/10.1158/1535-7163.MCT-10-0707
  20. Fidler IJ, Ellis LM. The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell 1994;79:185-8. https://doi.org/10.1016/0092-8674(94)90187-2
  21. Folkman J, Merler E, Abernathy C, Williams G. Isolation of a tumor factor responsible for angiogenesis. J Exp Med 1971;133:275-88. https://doi.org/10.1084/jem.133.2.275
  22. Folkman J, Klagsbrun M. Angiogenic factors. Science 1987;235:442-7. https://doi.org/10.1126/science.2432664
  23. Gospodarowicz D, Ferrara N, Schweigerer L, Neufeld G. Structural characterization and biological functions of fibroblast growth factor. Endocr Rev 1987;8:95-114. https://doi.org/10.1210/edrv-8-2-95
  24. Esch F, Baird A, Ling N, et al. Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proc Natl Acad Sci U S A 1985;82:6507-11. https://doi.org/10.1073/pnas.82.19.6507
  25. Jaye M, Howk R, Burgess W, et al. Human endothelial cell growth factor: cloning, nucleotide sequence, and chromosome localization. Science 1986;233:541-5. https://doi.org/10.1126/science.3523756
  26. Gospodarowicz D, Thakral KK. Production a corpus luteum angiogenic factor responsible for proliferation of capillaries and neovascularization of the corpus luteum. Proc NatlAcad Sci U S A 1978;75:847-51. https://doi.org/10.1073/pnas.75.2.847
  27. Vlodavsky I, Folkman J, Sullivan R, et al. Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci U S A 1987;84:2292-6. https://doi.org/10.1073/pnas.84.8.2292
  28. Matsuzaki K, Yoshitake Y, Matuo Y, Sasaki H, Nishikawa K. Monoclonal antibodies against heparin-binding growth factor II/basic fibroblast growth factor that block its biological activity: invalidity of the antibodies for tumor angiogenesis. Proc Natl Acad Sci U S A 1989;86:9911-5. https://doi.org/10.1073/pnas.86.24.9911
  29. Dennis PA, Rifkin DB. Studies on the role of basic fibroblast growth factor in vivo: inability of neutralizing antibodies to block tumor growth. J Cell Physiol 1990;144:84-98. https://doi.org/10.1002/jcp.1041440112
  30. Benjamin LE, Golijanin D, Itin A, Pode D, Keshet E. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest 1999;103:159-65. https://doi.org/10.1172/JCI5028
  31. Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascular-specific growth factors and blood vessel formation. Nature 2000;407:242-8. https://doi.org/10.1038/35025215
  32. Jain RK. Molecular regulation of vessel maturation. Nat Med 2003;9:685-93. https://doi.org/10.1038/nm0603-685
  33. Ferrara N. Vascular endothelial growth factor as a target for anticancer therapy. Oncologist 2004;9 Suppl 1:2-10. https://doi.org/10.1634/theoncologist.9-suppl_1-2
  34. Fontanini G, Vignati S, Boldrini L, et al. Vascular endothelial growth factor is associated with neovascularization and influences progression of non-small cell lung carcinoma. Clin Cancer Res 1997;3:861-5.
  35. Vaisman N, Gospodarowicz D, Neufeld G. Characterization of the receptors for vascular endothelial growth factor. J Biol Chem 1990;265:19461-6.
  36. Jakeman LB, Winer J, Bennett GL, Altar CA, Ferrara N. Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. J Clin Invest 1992;89:244-53. https://doi.org/10.1172/JCI115568
  37. Volm M, Koomägi R, Mattern J. Prognostic value of vascular endothelial growth factor and its receptor Flt-1 in squamous cell lung cancer. Int J Cancer 1997;74:64-8. https://doi.org/10.1002/(SICI)1097-0215(19970220)74:1<64::AID-IJC11>3.0.CO;2-I
  38. Brown LF, Berse B, Jackman RW, et al. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res 1993;53:4727-35.
  39. Brown LF, Berse B, Jackman RW, et al. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Hum Pathol 1995;26:86-91. https://doi.org/10.1016/0046-8177(95)90119-1
  40. Salameh A, Galvagni F, Bardelli M, Bussolino F, Oliviero S. Direct recruitment of CRK and GRB2 to VEGFR-3 induces proliferation, migration, and survival of endothelial cells through the activation of ERK, AKT, and JNK pathways. Blood 2005;106:3423-31. https://doi.org/10.1182/blood-2005-04-1388